18-22171999-G-T

Variant names:

• chr18-22171999-G-T
• rs1014349671
• NM_005257.6:c.855G>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_005257.6(GATA6):​c.855G>T​(p.Ala285Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,231,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (0 hom.)
• Consequence: GATA6 NM_005257.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.362

Genes affected

GATA6 (HGNC:4174): (GATA binding protein 6) This gene is a member of a small family of zinc finger transcription factors that play an important role in the regulation of cellular differentiation and organogenesis during vertebrate development. This gene is expressed during early embryogenesis and localizes to endo- and mesodermally derived cells during later embryogenesis and thereby plays an important role in gut, lung, and heart development. Mutations in this gene are associated with several congenital defects. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 18-22171999-G-T is Benign according to our data. Variant chr18-22171999-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 472918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.362 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000595 (90/151360) while in subpopulation NFE AF= 0.000828 (56/67666). AF 95% confidence interval is 0.000654. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 90 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA6	NM_005257.6	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 2 of 7	ENST00000269216.10	NP_005248.2
GATA6	XM_047437483.1	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 2 of 7		XP_047293439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA6	ENST00000269216.10	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 2 of 7	1	NM_005257.6	ENSP00000269216.3
GATA6	ENST00000581694.1	c.855G>T	p.Ala285Ala	synonymous_variant	Exon 1 of 6	1		ENSP00000462313.1

Frequencies

GnomAD3 genomes AF: 0.000595 AC: 90 AN: 151254 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.00578

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000827

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000971 AC: 1049 AN: 1080090 Hom.: 0 Cov.: 30 AF XY: 0.00100 AC XY: 511 AN XY: 510790

Gnomad4 AFR exome AF: 0.000133

Gnomad4 AMR exome AF: 0.000366

Gnomad4 ASJ exome AF: 0.00560

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000995

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000975

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.000595 AC: 90 AN: 151360 Hom.: 0 Cov.: 32 AF XY: 0.000500 AC XY: 37 AN XY: 73944

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.000526

Gnomad4 ASJ AF: 0.00578

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000828

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000476 Hom.: 0

Bravo AF: 0.000740

ClinVar

Significance: Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 31, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GATA6: BP4, BP7 -

GATA6-related disorder Benign:1

Jan 02, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Atrioventricular septal defect 5 Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1014349671; hg19: chr18-19751960;